A5006549305- Microtubule and mitosis dynamics
- Photosynthetic Processes and Mechanisms
- Protist diversity and phylogeny
- Cellular transport and secretion
- Plant nutrient uptake and metabolism
- Cellular Mechanics and Interactions
- Retinal Development and Disorders
- Genomics and Chromatin Dynamics
- Historical and Literary Analyses
- Linguistic Studies and Language Acquisition
- Chromosomal and Genetic Variations
- Italian Literature and Culture
- Hemoglobin structure and function
MRC Laboratory of Molecular Biology
2023-2024
Max Planck Institute of Molecular Physiology
2021-2023
The MAP kinase and motor scaffold JIP3 prevents excess lysosome accumulation in axons of vertebrates invertebrates. How JIP3's interaction with dynein kinesin-1 contributes to organelle clearance is unclear. We show that human light intermediate chain (DLIC) binds the N-terminal RH1 domain JIP3, its paralog JIP4, lysosomal adaptor RILP. A point mutation abrogates DLIC binding without perturbing between kinesin heavy chain. Characterization this separation-of-function Caenorhabditis elegans...
In metazoans, a ≈1 megadalton (MDa) multiprotein complex comprising the dynein-dynactin adaptor Spindly and ROD-Zwilch-ZW10 (RZZ) is building block of fibrous biopolymer, kinetochore corona. The corona assembles on mitotic kinetochores to promote microtubule capture spindle assembly checkpoint (SAC) signaling. We report here high-resolution cryo-EM structure that captures essential features RZZ complex, including farnesyl-binding site required for binding. Using highly predictive in vitro...
Cytoplasmic Dynein 1, or Dynein, is a microtubule minus end–directed motor. motility requires Dynactin and family of activating adaptors that stabilize the Dynein–Dynactin complex promote regulated interactions with cargo in space time. How limit activation to specialized subcellular locales unclear. Here, we reveal Spindly, mitotic adaptor at kinetochore corona, exists natively closed conformation occludes binding its CC1 box Spindly motif. A structure-based analysis identified various...
Chromosome biorientation on the mitotic spindle is prerequisite to errorless genome inheritance. CENP-E (kinesin-7) and dynein-dynactin (DD), microtubule motors with opposite polarity, promote from kinetochore corona, a polymeric structure whose assembly requires MPS1 kinase. The corona's building block consists of ROD, Zwilch, ZW10, DD adaptor Spindly (RZZS). How are scaffolded mutually coordinated in corona remains unclear. Here, we show that when prevented through inhibition, absolutely...
Abstract During cell division, NuMA orchestrates the focusing of microtubule minus-ends in spindle poles and cortical force generation on astral microtubules by interacting with dynein motors, microtubules, other cellular factors. Here we used vitro reconstitution, cryo-electron microscopy, live imaging to understand mechanism regulation NuMA. We determined structure processive dynein/dynactin/NuMA complex (DDN) showed that N-terminus drives motility facilitates dynein-mediated transport...
Cytoplasmic Dynein 1, or Dynein, is a microtubule minus-end directed motor. motility requires Dynactin and family of activating adaptors that stabilize the Dynein-Dynactin complex promote regulated interactions with cargo in space time. How limit activation to specialized subcellular locales unclear. Here, we reveal Spindly, mitotic adaptor at kinetochore corona, exists natively closed conformation occludes binding its CC1 box Spindly motif. A structure-based analysis identified various...
Chromosome biorientation on the mitotic spindle is prerequisite to errorless genome inheritance. CENP-E (kinesin 7) and Dynein-Dynactin (DD), microtubule motors with opposite polarity, promote from kinetochore corona, a polymeric structure whose assembly requires MPS1 kinase. The corona's building block consists of ROD, Zwilch, ZW10, DD adaptor Spindly (RZZS). How are scaffolded mutually coordinated in corona remains unclear. Here, we report near-complete depletion RZZS kinetochores after...
In metazoans, a ≍1 megadalton (MDa) super-complex comprising the Dynein-Dynactin adaptor Spindly and ROD-Zwilch-ZW10 (RZZ) complex is building block of fibrous biopolymer, kinetochore corona. The corona assembles on mitotic kinetochores to promote microtubule capture spindle assembly checkpoint (SAC) signaling. We report here high-resolution cryo-EM structure that captures essential features RZZ complex, including farnesyl binding site required for binding. Using highly predictive in vitro...
SUMMARY The conserved MAP kinase and motor scaffold JIP3 prevents excess lysosome accumulation in axons of vertebrates invertebrates. Whether how JIP3’s interaction with dynein kinesin-1 contributes to this critical organelle clearance function is unclear. Using purified recombinant human proteins, we show that light intermediate chain (DLIC) binds the N-terminal RH1 domain JIP3, its paralog JIP4, lysosomal adaptor RILP. A point mutation a hydrophobic pocket domain, previously shown abrogate...